Keratoconus is a bilateral, noninflammatory corneal ectasia with an incidence of approximately one per 2,000 in the general population, although less obvious cases such as early forme fruste presentations are thought to be much more common. Keratoconus is characterized by a progressive increase in corneal curvature, with apical thinning and irregular corneal astigmatism. Eventually, an obvious cone-shaped protrusion of the corneal surface may develop.

Keratoconus often becomes apparent during the teenage years and classically progresses until the third and fourth decades of life, when many affected individuals experience an arrest of disease progression or at least a reduction in the rate of progression.

Etiology

The pathophysiology of how keratoconus develops and progresses is not well understood. Genetic factors appear to be multifactorial and are considered fundamental to the etiology and progression of keratoconus. However, the underlying molecular and/or genetic abnormalities are unknown.

Keratoconus has been linked with systemic conditions such as atopic disease, genetic conditions such as trisomy 21 and Turner’s syndrome, and various connective tissue disorders, as well as with eye rubbing, rigid contact lens wear and ocular trauma. Keratoconic corneas also have an accumulation of cytotoxic by-products from the nitric oxide and lipid peroxidation pathways, abnormal antioxidant enzymes, and increased levels of mitochondrial DNA damage. These findings suggest that ongoing oxidative stress contribute to keratoconus.1

Signs and Symptoms

Early stage. Very early in the disease process, the visual impairment caused by keratoconus is usually correctable with soft contact lenses or spectacles. These patients may gain the attention of the ophthalmologist if progressive myopic astigmatism develops, particularly with steeper-than-average keratometry or topography readings. As the disease progresses, it is often increasingly difficult to refract the patient to a crisp and clear visual acuity with soft contact lenses or spectacles.

Intermediate stage. As the disease progresses to an intermediate stage, patients usually experience vision loss that is no longer correctable with soft contact lenses or spectacles. Toric soft lenses often help with correcting some of the astigmatism; however, the increasing irregularity of the astigmatism may call for rigid, gas-permeable contacts in order to achieve truly crisp vision. Some patients require a piggyback configuration consisting of hard contact lenses worn over soft lenses to achieve adequate fit, comfort and vision. If a young patient develops progressive astigmatism between examinations, this should alert the ophthalmologist that further corneal imaging may be needed to evaluate the patient for worsening keratoconus.

Advanced stage. For patients who progress to the more advanced stages of disease, contact lens wear may become increasingly difficult and often uncomfortable due to the steepness of the cornea and difficulty in fitting the lenses. Contact lens intolerance is a common indication for corneal transplantation at this stage.

Diagnosis

Early stage. Computerized corneal topography (CCT) techniques using curvature-based analysis and newer forms of elevation-based tomography appear to be the most sensitive methods for detecting early keratoconus.

Prior to these, the most sensitive methods included 1) apical decentration on the keratometer using the Soper topogometer, 2) subtle changes in the retinoscopic reflex that progress to early scissoring and 3) changes in the ability to visualize the endothelial specular reflection relative to the epithelial reflection during slit-lamp biomicroscopy.

Elements of earlier techniques— keratometry and Placido disk–based keratoscopy—have now been integrated into sophisticated, computerized systems capable of generating color-coded curvature and elevation maps. Even with these technological advances, it is increasingly recognized that elevation data using scanning slit or Scheimpflug imaging provides data that are diagnostically very helpful when screening patients with possible corneal ectasia.

A number of diagnostic algorithms can help diagnose early keratoconus; however, there remains no universally agreed-upon diagnostic criterion that, by itself, conclusively diagnoses the earliest cases. Typically, changes in elevation relative to a best-fit sphere occur on the posterior corneal surface more rapidly than similar changes are seen on the anterior surface. Other findings include apical decentration, corneal thinning, increasing irregular corneal astigmatism, and Rizzutti’s sign, which is a sharply focused conical reflection obtained on the nasal cornea after a penlight is shone on the temporal side.

Intermediate stage. Even in patients with intermediate-stage disease, corneal changes may still be subtle and not readily apparent by slit-lamp biomicroscopy alone. The retinoscopic streak usually demonstrates scissoring, and it is hard to neutralize the streak reflection during refraction. Computerized corneal topography and elevation-based tomography—Orbscan IIz (Bausch & Lomb) and Pentacam (Oculus) are probably the most widely used—typically demonstrate findings that are usually more obvious with regard to both diagnosis and monitoring disease progression.

Corneal hydrops. Occasionally, patients can progress to acute corneal hydrops, a stromal edema caused by aqueous penetration through breaks in Descemet’s membrane. The onset of corneal hydrops is classically associated with a sudden decrease in both uncorrected and corrected vision as well as redness, pain and photophobia. The corneal edema may persist unpredictably for weeks or months, with gradual resolution as the posterior break is replaced with a posterior collagenous scar. Topical osmotic agents such as hypertonic saline may accelerate the recovery of vision; however, this treatment is most helpful to alleviate edema within the epithelium and anterior stroma.

Treatment

There are no drugs known to reverse or prevent keratoconus, but patients may be able to slow its progression by refraining from rubbing their eyes. When spectacles or contacts are no longer effective, there are several surgical options, including the following:

Penetrating keratoplasty. Full-thickness penetrating keratoplasty (PK) is the treatment most commonly offered. Nearly 95 percent of these procedures maintain a clear and functioning graft at five years. The rejection rate appears to be lower than that seen in patients undergoing PK for other indications. In spite of successful surgery, residual corneal astigmatism and refractive error often limits the corrective power of spectacles and usually requires additional correction with a contact lens. In addition to irregular astigmatism, complications after PK can include allograft rejection, a fixed, dilated pupil and, on occasion, recurrence of keratoconus. What causes recurrence is unclear; it may represent underlying disease in the donor or possibly progression of disease.

Lamellar keratoplasty. For patients who have moderate keratoconus without significant scarring, there is renewed interest in lamellar keratoplasty, especially with the precision, predictability and convenience of the femtosecond laser for these cases.

Corneal ring segments. Corneal stromal ring segments (Intacs, Addition Technology) are also an option, particularly if the patient demonstrates disease progression with apical displacement. These ring segments consist of two 150-degree PMMA arcs that are inserted surgically into the cornea through a small 1.8- to 2-mm radial incision created in the steep axis. Adding ring segment thickness to the midperipheral corneal stroma produces an “arc shortening,” effectively flattening the central cornea. This results from the corneal lamellae extending from limbus to limbus in a continuous fashion with a new alteration in corneal curvature that is in proportion to the ring thickness. The thin, ectatic, keratoconic cornea is particularly amenable to this effect.

Complications have primarily been associated with the insertion technique, but technique has improved greatly due to the use of new equipment designed to reduce the risk of poor ring placement. Although the ring segments lack great predictability, most properly selected patients experience some improvement in their uncorrected vision and may regain contact lens tolerance due to improved corneal topography.

Recent studies have shown that Intacs corneal ring segment implantation is a safe and effective treatment for keratoconus, with significant and sustained improvements in vision as well as improved contact lens tolerance.2 Studies have also compared placement of single-ring with double-ring segments. In some cases, the single-ring segment offers improved astigmatic correction, but the evidence is not conclusive.3 Studies are also under way examining the combination of ring segments with collagen cross-linking using riboflavin activated by ultraviolet irradiation.

Contraindicated surgeries. LASIK remains contraindicated in patients with keratoconus due to the possible risk of accelerating the ectasia. Surface ablation photorefractive keratectomy procedures are also considered contraindicated in patients with known keratoconus; however, this surgery is currently under study in patients with early disease that is considered stable or slowly progressive.

Mr. Gupta is a third-year medical student at Ross University in Dominica. Dr. Carlson is professor of ophthalmology and chief of the cornea and refractive surgery service at Duke University. Neither author has a proprietary or financial interest in any product mentioned in this article.